# US 2021/0275587 A1 · Mitochondrial augmentation therapy of renal diseases

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- Number: US 2021/0275587 A1
- Document ID: US20210275587A1
- Status: Published application
- Kind: A1
- Application number: 17/251,666
- Filed: 2019-07-22
- Published: 2021-09-09
- Earliest claimed: 2018-07-22
- Assignees: Minovia Therapeutics Ltd.
- Applicants: Minovia Therapeutics Ltd.
- Inventors: Natalie Yivgi Ohana; Uriel Halavee; Shmuel Bukshpan; Moriya Blumkin; Noa Sher
- Web page: https://patentgrep.com/patent/US20210275587A1

## CPC

- A61K 35/15: Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells (presenting a specific antigen A61K39/00; therapeutic combinations of antibodies, or fragments thereof, and blood-derived cells A61K39/00)
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 35/18: Erythrocytes (haemoglobin A61K38/42)
- A61K 35/19: Platelets; Megacaryocytes
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 35/33: Fibroblasts
- A61K 35/35: Fat tissue; Adipocytes; Stromal cells; Connective tissues (adipose-derived stem cells A61K35/28; collagen A61K38/39)
- A61K 35/38: Stomach; Intestine; Goblet cells; Oral mucosa; Saliva
- A61K 35/545: Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
- A61P 13/00: Drugs for disorders of the urinary system
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention provides stem cells enriched with healthy functional mitochondria, pharmaceutical compositions comprising these cells and methods of use thereof for treating renal diseases, disorders and symptoms thereof where the disease may or may not be associated with acquired mitochondrial dysfunction.

## Claims

### Claim at position 1

-3. (canceled)

### Claim 4 (depends on 28)

The method of claim 28, wherein the exogenous mitochondria are syngeneic or allogeneic.

### Claim at position 3

-6. (canceled)

### Claim 7 (depends on 28)

The method of claim 28, wherein the disease or disorder is selected from the group consisting of nephropathy, nephritis, nephrosis, nephritic syndrome, nephrotic syndrome, Fanconi's syndrome and kidney failure.

### Claim 8 (depends on 28)

The method of claim 28, wherein the symptom is selected from the group consisting of low blood alkaline phosphatase levels, low blood magnesium levels, high blood creatinine levels, low blood bicarbonate levels, low blood base excess levels, high urine glucose/creatinine ratios, high urine chloride/creatinine ratios, high urine sodium/creatinine ratios, high blood lactate levels, high urine magnesium/creatinine ratios, high urine potassium/creatinine ratios, high urine calcium/creatinine ratios and high blood urea levels.

### Claim at position 6

-12. (canceled)

### Claim 13 (depends on 28)

The method of claim 28, wherein the mitochondrially-enriched human stem cells have at least one of:
an increased mitochondrial DNA content;
(ii) an increased level of citrate synthase (CS) activity;
(iii) an increased content of at least one mitochondrial protein selected from SDHA and COX1;
(iv) an increased rate of 02 consumption;
(v) an increased rate of ATP production; or
(vi) any combination thereof, relative to the corresponding level in the stem cells prior to mitochondrial enrichment.

### Claim at position 8

-16. (canceled)

### Claim 17 (depends on 28)

The method of claim 28, wherein the human stem cells are hematopoietic stem cells, mesenchymal stem cells, pluripotent stem cells (PSCs), induced pluripotent stem cells (iPSCs), or CD34+ cells.

### Claim at position 10

-21. (canceled)

### Claim 22 (depends on 28)

The method of claim 28, wherein the human stem cells are isolated, derived or obtained from cells of the bone marrow, adipose tissue, oral mucosa, skin fibroblasts, blood or umbilical cord blood.

### Claim 23 (depends on 28)

The method of claim 28, wherein the human exogenous mitochondria are isolated or obtained from placenta, placental cells grown in culture or blood cells.

### Claim 24

(canceled)

### Claim 25 (depends on 28)

The method of claim 28, wherein the human exogenous mitochondria constitute at least 1-30% of the total mitochondria in the mitochondrially enriched human stem cells.

### Claim 26 (depends on 25)

The method of claim 25, wherein the human exogenous mitochondria constitute at least 1%, 3%, 5%, 10%, 15%, 20%, 25% or 30% of the total mitochondria in the mitochondrially enriched human stem cells.

### Claim 27 (depends on 28)

The method of claim 28, wherein the composition further comprises non-enriched stem cells, megakaryocytes, erythrocytes, mast cells, myeloblasts, basophils, neutrophils, eosinophils, monocytes, macrophages, natural killer (NK) cells, small lymphocytes, T lymphocytes, B lymphocytes, plasma cells, reticular cells, or any combination thereof.

### Claim 28

A method of treating a renal disease, disorder or a symptom thereof in a human patient in need of such treatment comprising administering parenterally a pharmaceutical composition to the patient, the pharmaceutical composition comprising at least about 5×105 to 5×109 human stem cells, wherein the human stem cells are enriched with human exogenous mitochondria, and wherein the renal disease or disorder is not a primary mitochondrial disease or disorder caused by a pathogenic mutation in mitochondrial DNA or by a pathogenic mutation in nuclear DNA encoding a mitochondrial protein.

### Claim 29 (depends on 28)

The method of claim 28, wherein said administering the pharmaceutical composition is directly to the renal system.

### Claim 30 (depends on 28)

The method of claim 28, wherein said administering the pharmaceutical composition is by systemic administration.

### Claim 31 (depends on 28)

The method of claim 28, wherein the human stem cells are obtained or derived from the patient before enrichment with the exogenous mitochondria.

### Claim 32 (depends on 28)

The method of claim 28, wherein the human stem cells are obtained or derived from a donor different than the patient before enrichment with the exogenous mitochondria.

### Claim 33 (depends on 32)

The method of claim 32, wherein the donor is at least partly HLA-matched with the patient.

### Claim 34 (depends on 32)

The method of claim 32, further comprising a step of administering to the patient an agent which prevents, delays, minimizes or abolishes an adverse immunogenic reaction between the patient and the mitochondrially-enriched human stem cells.

### Claim 35 (depends on 34)

The method of claim 34, wherein the adverse immunogenic reaction is a graft-versus-host disease (GvHD).

### Claim 36 (depends on 28)

The method of claim 28, further comprising administering to the subject non-enriched stem cells, megakaryocytes, erythrocytes, mast cells, myeloblasts, basophils, neutrophils, eosinophils, monocytes, macrophages, natural killer (NK) cells, small lymphocytes, T lymphocytes, B lymphocytes, plasma cells, reticular cells, or any combination thereof.

### Claim 37 (depends on 13)

The method of claim 13, wherein increased mitochondrial DNA content is from endogenous and/or exogenous mitochondria.

### Claim 38 (depends on 26)

The method of claim 26, wherein the human exogenous mitochondria constitute at least 1% of the total mitochondria in the mitochondrially enriched human stem cells.